The interaction of catecholamines with Beta-adrenergic receptors leads to an increase in the activity of the enzyme adenylate cyclase. A direct "in vitro" assay for these receptors using 125 I-hydroxybenzylpindolol will be used to study some of the factors which regulate either the density or properties of Beta-receptors in rat brain and liver and in several lines of cells maintained in tissue culture. In addition to measuring binding sites the responsiveness of adenylate cyclase to catecholamines will be determined. An autoradiographic assay for Beta-adrenergic receptors will be established and used to determine the cellular and regional distribution of the receptors. The ontogenetic pattern of Beta-adrenergic receptors and the effects of drugs on normal development will be studied in homogenates of cerebral cortex. Pharmacological agents which affect the concentration, synthesis, metabolism or reuptake of norepinephrine have profound effects on behavior and in some cases these agents have been shown to affect hormone sensitive adenylate cyclase. The effects of these drugs on the properties of Beta-adrenergic receptors and hormone sensitive adenylate cyclase will be determine in these experiments. In other experiments the effects of hormone administration and of adrenalectomy, hypophysectomy, and castration will be investigated. These systems will be used to study the regulation of the synthesis and degradation of Beta-adrenergic receptors. A series of experiments will also be carried out using cell lines derived from brain and liver. The primary focus of these experiments will be on the mechanism of desensitization, the inheritance of Beta-adrenergic receptor mediated responses, and the relationship between Beta-adrenergic receptors and cyclic AMP production. It is hoped that these experiments will have implications both in terms of the basis and therapy of mental disease and in terms of the regulation of adrenergic receptors by hormones and by catecholamines.